Nanoparticles and macroparticles, including nanocapsules, have been investigated as carriers for drug delivery. Development of new particles that can effectively protect therapeutic agents from premature degradation in order to increase bioavailability are still needed, however.
Bendamustine, 4-{5-[bis(2-chloroethyl)amino]-1-methyl-2-benzimidazolyl} butyric acid has the following formula:

Bendamustine hydrochloride was initially synthesized in 1963 in the German Democratic Republic (GDR) and was available from 1971 to 1992 there under the tradename Cytostasan®. See, e.g., W. Ozegowski and D. Krebs, IMET 3393 γ-[1-methyl-5-bis-β-chloroethyl)-aminobenzimidazolo-(2)]-butyryl chloride, a new cytostatic agent of the group of benzimidazole nitrogen mustards. Zbl. Pharm. 110, (1971) Heft 10, 1013-1019, describing the synthesis of bendamustine hydrochloride monohydrate. Since that time, it has been marketed in Germany under the tradename Ribomustin®. Bendamustine is an alkylating agent that has been shown to have therapeutic utility in treating diseases such as chronic lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. Bendamustine hydrochloride is marketed in the United States under the tradename Treanda®.
While bendamustine has demonstrated efficacy, it is known to be unstable, especially in aqueous solutions, leading to technical difficulties in its preparation and administration. As a result, bendamustine hydrochloride has only been marketed as a lyophilized preparation that is reconstituted immediately prior to infusion. In addition, because of this instability in an aqueous environment, the drug has a relatively short-half life, which limits the suitability of the current formulations for treating certain types of solid tumors. Because of the limitations associated with the currently available formulations, the expansion of the therapeutic use of bendamustine has been limited. New formulations of bendamustine are needed.